Quality Standards for Medical Honey

on Sunday, 21 April 2013. Posted in Honey Research

Honey has been in continuous use for wound care since the most ancient times, but went out of common use...

Honey has been in continuous use for wound care since the most ancient times, but went out of common use in the medical profession when antibiotics came into use in the 1940s. Its coming back into mainstream practice has primarily resulted from the discovery of the unusual antibacterial properties of honey from some Leptospermum species (manuka).

Although honey used in wound care prior to that was unselected and was the same quality as honey used as food, modern clinical practice has required assurance of the safety of honey used in wound care, hence the concept of ‘medical grade honey’ has come into being.

Although honey is primarily produced by a form of agriculture, termed apiculture, rather than gathered from wild hives, there is little control possible over its production. Its actual production, drop by drop, is by bees ranging free in the environment over distances of several kilometers to harvest nectar. This means that bees could be bringing in potentially harmful materials in that nectar from sources that is unknown. There is further scope for contamination of honey within the hive and during the collection of the honey combs from the hives and the extraction of the honey from these. The ways in which such contamination could occur, and the ways of minimizing the risks, are covered in the sections below.

It will be seen by reading on that honey suitable for use as an ingredient for a ‘medical device’ can only be obtained via skilled and experienced apiculturists who have been educated about the many special considerations and requirements for such production, and not by purchase of honey on the ‘spot market’.

The Nature of Honey
The Codex Alimentarius produced by the Food and Agriculture Organisation of the United Nations defines honey as "the natural sweet substance produced by honey bees from nectar of blossoms or from secretions of living parts of plants or excretions of plant sucking insects on the living parts of plants, which honey bees collect, transform and combine with specific substances of their own, store and leave in the honey comb to ripen and mature". Honey is a highly concentrated solution of a complex mixture of sugars. Depending on the floral source of the nectar, glucose in honey may be at a level in which it supersaturates in solution so crystals of glucose monohydrate may form and be suspended in the syrupy solution. These will dissolve if honey gets diluted (e.g. by wound exudate) or if it is warmed. The sugars in honey are primarily glucose and fructose, normally with more fructose than glucose, but the sugar composition varies depending on the source of the nectar. The average composition of 490 samples of honey from the USA was found to be 79.6% sugars and 17.2% water.

Honey may also have suspended in it other particles besides glucose crystals. In extracted honey there may be particles of wax from the honey comb, pollen from flowers incorporated in the honey or introduced during its extraction and debris such as bees' knees picked up on the comb in the beehive. The incorporation into wound tissue of particles from honey which are not biodegradable is likely to give a ‘foreign body reaction’ and lead to a granule being formed. The aim with medical grade honey is to remove as much as possible of the particulate matter by filtration (see below) and with efficient wax removal systems. Honey contains a quantitatively small amount of pollen, but there is a possible risk of allergic reaction to it. However, allergic reactions to honey (reported as food allergies) are rare. But these have been attributed in about half of the cases to a reaction to a specific pollen in the honey, the rest to bee proteins in honey. The content of bee proteins in honey cannot be avoided and would be expected to be fairly constant since the bees add the proteins to the honey as a secretion from the hypo pharyngeal gland during collection of nectar and when processing the honey in the hive. The content of pollen, however, can be minimized, so the aim in producing medical grade honey should be to have the pollen content as low as possible.

Honey normally contains between 2,000 and 10,000 pollen grains per gram, which is equivalent to 0.006% – 0.03% w:w of the honey, and this can be reduced to even lower levels by filtration of honey. The practice of some processors the authors are familiar with for preparation of medical grade honey involves the use of a heat exchanger to allow the honey to be heated for as a short a period of time as possible to decrease the viscosity of honey to allow filtration through the finest filters practicable. Heating is also required to dissolve the coarse glucose crystals which form in extracted honey. To avoid coarse crystals of glucose re-forming from uncontrolled crystal growth in the super-saturated solution formed when they have been dissolved by heating, honey for medical use is usually turned into a ‘creamed’ form by having the crystal growth seeded with a large number of very fine crystals of glucose obtained by grinding some crystallised honey. The subsequent growth of the crystals is allowed to occur at 14°C to get well dispersed small crystals that give the honey a smooth texture.

Excessively long heating may occur if honey is heated in bulk for processing, and the honey may remain at fairly high temperatures for a further long period as it cools afterwards. There are adverse effects on the honey when it is heated to high temperatures or kept too long at an intermediate temperature: the enzyme which produces hydrogen peroxide gets inactivated, and toxic substances such as hydroxymethyl furfural (HMF)and 3-deoxyglucosone (3-DG) are formed.

Because the pollen grains from some species of plants are very small they are likely to pass though the finest filters that can be used with such a viscous fluid as honey. (Pollen grains are in the range of 5 - 200 µm in diameter – medical grade honey is typically filtered though a 50 µm mesh.) Thus the aim with honey produced for medical care is to minimise the content of pollen in honey prior to filtration, as well as minimise the contamination with other particulate matter which may be too small to remove by filtration. Partly this is achieved by treating honey as a medical product right from the point of removal of the combs from the hives, ensuring the cleanest possible handling practices. But also there are procedures that can be used in extracting the honey from the combs that are different from those used in normal honey processing. These will greatly minimise inclusion of pollen and other particulate matter in the extracted honey.

Very little pollen gets into the nectar which the bees pack into the cells in the comb to make honey. Some pollen may possibly fall into the nectar held in flowers, but mostly it gets in from the mouth parts of the ‘house bees’ which process in the hive both the nectar and pollen harvested by foraging worker bees. The bulk of the pollen harvested, which is used as a source of protein for the colony, is stored in the brood comb, but some is also stored in pollen cells interspersed with honey cells in honey comb. When honey is extracted by crushing the combs, or when a ‘loosening’ device is used before extraction to liquefy manuka honey which is a thixotropic honey (commonly done by plunging a sheet of needles repeatedly into the comb), the honey becomes contaminated with pollen from any pollen storage cells in the comb). This can be prevented by not including any honey comb containing pollen cells when the honey is extracted for use as a medical product.

Honey is normally removed from the comb by cutting off the caps from the cells with a knife or some form of mechanical device before centrifuging the comb to get the honey out. The capped surface of the combs has on it a lot of pollen that has fallen off bees working on the combs, and also has on it debris from dead bees. The salvaging of honey cut off with the ‘capping’ by draining or centrifuging the ‘capping’ is normal practice but this introduces debris and extra pollen into honey. So for medical grade honey such salvaged honey should not be added to the extracted honey being processed.

The widespread practice in apiculture of re-using the emptied comb for production of the following season’s honey crop is another common source of contamination. Pollen remains in the comb, especially in the pollen cells, when the comb is drained or centrifuged. This pollen will end up in the new honey that the bees pack into the comb. New ‘foundation’ comb is required in hives each season when medical grade honey is produced.

Safety of Honey
Medical devices containing honey are manufactured under the same regulations as any other ‘medical device’. The processing of the raw ingredient is also regulated. But the actual production of the raw ingredient is done in the wild, so the only control of quality possible there is though good beekeeping practices by apiarists. With many thousands of bees out foraging from a hive, nobody knows which plants they are visiting to collect nectar. It is essential that beekeepers are fully familiar with the sources of nectar available to their bees within a few kilometers of an apiary site, so that they can identify and avoid potential sources of contamination of honey produced as an ingredient for ‘medical devices’. It is also essential that they take great care with the hives in which medical grade honey is produced and with the honey when it is removed and transported to where it is processed.

Risks of Contamination by Chemicals
Some plants produce toxic nectar, so it is important that beekeepers are fully aware of the location of such plants so that hives are not placed close enough for bees to visit them at the time of year when nectar or honeydew could be collected from them. Commonly known sources of toxic honey are rhododendron (Rhododendron spp.) and tutu (Coriaria arborea) which produce neurotoxins, and vipers bugloss (Echium vulgare) which produces an alkaloid which damages the liver. These sorts of toxins would not be expected to affect wound repair and regeneration, but can easily be kept out of honey by good beekeeping practice, not allowing production of medical grade honey in regions or at times of the season when bees could collect toxic nectar or honeydew. Experienced professional beekeepers are well aware of these risks.

Another potential source of toxic chemicals which could get into honey via nectar collected by bees is residues on plants that have been sprayed with herbicides, insecticides or fungicides. Certified organic honey should have had inspection to ensure that no such contamination of the honey could occur as a result of spraying in the surrounding environment. In the production of manuka honey such contamination is generally unlikely because the manuka trees grow as a wild forest. It is only on the edges of such forests that there is a risk of contamination of the honey through nectar collected from adjacent farm land or plantation forests. To avoid this risk beekeepers need to inspect apiary sites to ensure that there is no likelihood of bees picking up agricultural chemicals from farmland within flying distance or where spray drift could occur.

A further possibility of contamination of honey is from chemicals used in apiculture. There are several risks of getting contamination of honey with these chemicals, all which can be avoided by good beekeeping practices. Some beekeepers use benzaldehyde as a bee repellent to get bees off the honey combs as they are removed from the hive. For production of medical grade honey an air blower should be used instead. For control of varroa mites miticide strips are placed in hives at certain times of the year. To avoid any possibility of the miticide getting into honey, the strips should never be used in hives when there is honey in the hives. The same applies to antibiotics used to treat bee diseases, as residues of these in honey used in wound care could encourage the development of antibiotic-resistant strains of bacteria in wounds. In manuka honey there is no risk of antibiotic residues, as New Zealand is free from the bee diseases for which antibiotics are used. A further possible source of contamination is from para-dichlorobenzene (PDCB) which is used to keep away wax moths from emptied honey combs being stored over winter for re-use in the next season. The risk of this chemical being in medical grade honey can be avoided by using only new ‘foundation’ comb each season. Traditional ‘foundation’ is made from wax melted down from emptied honeycomb. Because PDCB dissolves in wax the ‘foundation’ produced could be contaminated. To avoid this risk for production of medical grade honey the foundation should be made from plastic, not wax.

Another possible source of chemical contamination of honey is from the re-use of containers (such as 200 litre drums) for the extracted honey. For this reason, when extracted from the comb, medical grade honey should be packed into new drums, with a new food-grade lining, or into new food-grade polyethylene buckets. The drums or buckets should be sealed in such a way that any liquid spilled on them cannot possibly seep into the honey inside or enter when opening the seal later.

Risks of Microbial Contamination
The enzymic production of hydrogen peroxide during the ripening of honey in the comb serves to sterilize the honey sealed in the cells of the comb, and is capable also of killing spores. The risks from microbial contamination of honey arise from honey getting contaminated during and after extraction from the comb. Honey commonly contains pollen and yeasts, bacteria, bacterial and fungal spores and fungal hyphae. Unless honey has been recently contaminated with bacteria, the vegetative bacterial cells in it will be dead. The high sugar content of honey is sufficient to achieve this. But spores introduced into extracted honey are not killed, because there is insufficient unbound water available in fully ripened honey for the enzyme that produces hydrogen peroxide to be active. There are risks to the patients’ health from using honey that has not been sterilized, because honey occasionally contains spores of Clostridia. The spores will not germinate in undiluted honey, but if honey is diluted by wound exudates they could germinate. They are strict anaerobes so will grow only in areas of necrosis, where atmospheric oxygen is excluded. The risks arising from Clostridia growing in such areas of wound tissue after being introduced from honey are the development of gangrene and wound botulism.

But there is no risk of such infections if the honey used is a wound-care product registered as a ‘medical device’: regulations require that these be sterilized. This is usually done by gamma-irradiation so that the antibacterial activity of the honey is not destroyed. However, gamma-irradiation does not destroy bacteria, it just kills them. There can still be an inflammatory response to their antitoxins, so a sterile product containing a large number of dead bacteria can be pyrogenic. For this reason, one of the quality standards for medical grade honey should be that the honey contains a low number of bacteria. Because the number of bacteria present in honey cannot be counted once the bacteria have been killed (other than an indirect estimate from measurement of pyrogens in honey), the counting has to be done as viable bacteria (‘colony-forming units’, cfu) in a plate count of honey before it is sterilized. This count of cfu is also important for ensuring that the honey will actually be sterilized by the radiation dose used: the achievement of sterility with the dose being used is validated with honey with a known cfu count. If honey has a higher number of bacteria present then the dose of radiation may not be sufficient to kill all of the bacteria.

The cfu counts from honey samples can vary from zero to tens of thousands per gram of honey (Snowdon and Oliver, 1996). Most samples of honey contain detectable levels of yeasts, although yeast counts are commonly below 100 cfu/g (Snowdon and Oliver, 1996). Bacteria do not grow in honey because of the high sugar content but osmophilic yeasts can grow to very high numbers in honey which has a high water content. Medical grade honey should have a maximum permitted water content specified that is below the level at which osmophilic yeasts can grow. Bacterial spores, particularly those in the Bacillus genus, are regularly found in honey (Snowdon and Oliver, 1996). These are the bacteria which are primarily responsible for the colonies that form in a plate count, because species of bacteria which do not form spores will not have survived the high sugar content of honey. The Bacillus spores most probably come from dead bees in the hive. Some unpublished work by one of the authors (PM) investigating this possibility supported this hypothesis. Samples of manuka honey sent in to a major processor were obtained which had come from beginner and part-time beekeepers. Samples of manuka honey were also obtained from experienced large-scale beekeeping businesses. Successful beekeeping businesses have to keep their colonies of bees in the hives healthy. The plate counts in the samples from the professional beekeepers ranged from zero to 50 cfu/g. In the honey from the non-professional ones the counts were much higher, ranging up to account higher than the maximum permitted in hone for sale as a food (100,000 cfu/g). This illustrates the point made above that honey suitable for medical use cannot be obtained on the spot market.

Like with other potentially harmful contaminants, the risk of getting the quality of medical grade honey compromised by microbes can be decreased by good apicultural practices. Honey is produced in rural environments. Soil is a rich source of microorganisms, as well as other particulate contaminants. Good apicultural practice in the production of medical grade honey is to ensure that the honey taken from the hives out in the field is protected from contact with soil or wind-blown dust. Also, combs in which the production of honey has not been completed should not be included when honey for medical use is collected from the hive, so as to avoid the growth of yeasts in the honey which has a high water content because the bees have not finished drying it off. As well as having the potential to cause chemical contamination, as mentioned above, re-use of emptied honey combs also has the potential to cause microbial contamination of honey.

Other sources of microbial contamination are post-harvest factors that influence any food product. These can be controlled by good manufacturing practices (GMP) where honey is extracted from the combs, filtered and packed in buckets or drums. The sources of contamination here include air-borne microbes, process workers, pests such as rodents and insects, equipment and buildings. GMP protocols should include the need for: filtered air, with the building under positive pressure so that unfiltered outside air cannot come in; clean outer clothing and hair covering, which does not go outside the clean processing area where it could get contaminated; scrupulous hand-washing by processing staff; a pest management programmed to keep the premises clear of rodents and insects; suitable storage facilities to ensure that containers into which honey will go cannot get contaminated. The importance of keeping the boxes of honey combs clean when taken off the hives and transported to the processing facility should be obvious here, as they are clearly a way in which dirt can be introduced into otherwise clean handling facilities.

The good beekeeping and honey processing practices outlined above that can be used to minimise the various potential risks arising from using honey in wound-care products should be a mandatory part of the quality standards set for any suppliers of honey as an ingredient for any honey product sold as a ‘medical device’. It is mostly up to the manufacturers of ‘medical devices’ to set the quality standards of the ingredients that they use. The authors are aware that some manufacturers do set such standards. But there are now many honey products coming on the market. Clinicians with concerns about the safety of the honey used should question manufacturers about the standards they set for the production and processing of the honey. Table 1 lists the quality standards set by at least one company for medical grade honey. Seeing as these standards are achievable, clinicians should expect such standards for the honey in all medical devices containing honey.

Standardizing Antibacterial Activity of Honey
At present the major reason why clinicians choose to use honey for wound care is because of its antibacterial activity. (This may change as they become more aware of other bioactivities of honey such as its anti-inflammatory activity, its stimulation of autolytic debridement and it stimulation of growth of wound repair tissues.) But the potency of the antibacterial activity of honey can vary up to 100-fold. For this reason there is a need to have quality standards with respect to the antibacterial activity of medical grade honey.

There are various ways in which the potency of antibacterial activity can be assessed. One is to count the number of bacteria staying alive after a set period of exposure of a bacterial culture to a set concentration of the antibacterial agent. Another is to find the minimum concentration of the antibacterial agent that is needed to inhibit the growth of a bacterial culture: this is known as the minimum inhibitory concentration (MIC). But the way that is most relevant to treating infected wounds is an agar diffusion assay, as this mimics the antibacterial agent diffusing into infected wound tissues. It also removes the complication of the potency of antibacterial activity of honeys other than manuka being related in a very complex way to the degree of dilution of the honey. The complexity is due to the fact that the antibacterial agent being assayed is hydrogen peroxide, but there is no hydrogen peroxide in undiluted honey: the enzyme that produces it does not become active until honey is diluted, the activity of this enzyme increasing as more water becomes available by greater dilution, but the same time becoming less active as the substrate for its reaction becomes diluted.

The agar diffusion assay gives an easily measured zone of inhibition around where the antibacterial agent under test is applied. The area of this zone is proportional to the potency of the antibacterial activity of the agent. By including in the assay some solutions of a standard antibacterial agent it is possible to express the antibacterial activity of the agent under test relative to that of a standard.

The antibacterial activity of manuka honey used in wound-care products is measured by reference to the standard antiseptic phenol, using an agar diffusion assay as described by Allen. This assay has the enzyme catalase added to the honey in order to destroy any hydrogen peroxide present, so that the measurement obtained is only of the non-peroxide antibacterial activity which is unique to manuka honey. (It is important when carrying out this assay to check that the catalase has sufficient activity by including a non-manuka honey which has a high activity due to hydrogen peroxide. If the enzyme has insufficient activity then honeys other than manuka honey will appear to have non-peroxide activity like manuka honey does. Different manufacturers set their own quality standards for the antibacterial activity of honey, so users should enquire what these are.

For honey in modern wound management it is important to avoid confusion and make healthcare practitioners aware that although all honeys share the same basic chemistry they are not as generic as other antibacterial agents e.g. silver. Efficacy of honey in a wound environment is a major consideration and manuka honey is proven to retain its antibacterial properties in a wound environment where other honeys probably will not because the production of hydrogen peroxide ceases after a day or so. There are known to be variances in antibacterial potency and therapeutic benefits between honeys from different floral sources and in order for there to be meaningful comparative data between clinical trials on honey it is important for authors to state the specific type of honey used and the level of its antibacterial activity.

Regulatory Requirements
Honey and honey dressings sold for use in wound care are classified as a ‘medical device’. DIRECTIVE 2007/47/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 September 2007, which amended the COUNCIL DIRECTIVE 93/42/EEC of 14 June 1993 concerning medical devices, define a ‘medical device’ as:

Any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings for the purpose of:

• Diagnosis, prevention, monitoring, treatment or alleviation of disease

• Diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap

• Investigation, replacement or modification of the anatomy or of a physiological process

Control of conception

And which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means.

The Medicines and Healthcare products Regulatory Agency (MHRA) is a body of the UK Government which was set up in 2003 to bring together the functions of the Medicines Control Agency (MCA) and the Medical Devices Agency (MDA).

These include the regulation of medicines and medical devices and equipment used in healthcare and the investigation of harmful incidents. The principal aim of the Agency is to safeguard the public’s health. It does this by making sure that medicines and medical devices work properly, perform their intended functions and are acceptably safe.

Is Honey Safe?
The MHRA advise that no product is 100 per cent safe, because all products that interact with the body have the potential for side effects. Depending on the nature of the device or medicine these may be very minor, but they may also be serious and therefore warrant extensive clinical evidence to establish the risk factors.

The key questions for the MHRA are:

Do the advantages outweigh the disadvantages of taking the medicine?
Does the medicine do the most good for the least harm for most people who will be taking it?
Are the side effects acceptable?

A high level of side effects may be acceptable for a medicine used to treat a life-threatening illness, for example, but not in one used for a common minor ailment. Ultimately, patients and their healthcare professionals have to weigh up the risks and advantages of each medicine or treatment regimen when determining the most appropriate treatment. Decisions are generally based the product indications, evidence provided from clinical study data, contra-indications and patient factors.

The safety of honey was discussed in the previous edition of this book (Molan, 2005) and it was concluded that honey is extremely safe to use. In over 500 wound care case studies and 140 cases of using honey in ophthalmology, there has been no mention of adverse effects, other than in some cases a small increase in pain. (The pain is caused by the acidity of honey giving a response in nocioceptors which have been sensitised by inflammation.) Honey is generally contra-indicated for people with allergies to bee products and venom.

As a wound management product honey must be tested for:

• Cytotoxicity
• Skin sensitization
• Skin irritation and where it is used on breached or compromised surfaces
• Sub-chronic toxicity

Genotoxicity
Honey must also pass the sterilization validation and stability tests in order to be a classed as a ‘medical device’.

It is well documented and cited that honey has been used to treat wounds for centuries; as far as the authors are aware no harmful side effects have been documented. However, in a safety-conscious medical devices market there is no room for complacency. For this reason a medical standard for honey has been established and is constantly being reviewed in order to achieve improvements. This standard addresses all the risk factors associated with management of bee hives and extraction of honey for wound care. Healthcare practitioners must be satisfied in all aspects of honey production, safety and efficacy. If these considerations are not fully addressed by the industry clinicians will not widely accept honey as a credible alternative therapy for wound management. To support this, manufacturers should declare the type of the honey and ensure the relevant standards are being met and honey production is being driven from a ‘medical device’ perspective.

Risk Assessment
The requirements of ISO14971:2007(E) provide manufacturers with a framework to systematically manage risk associated with the use of a ‘medical device’. It is the manufacturer’s responsibility to fully assess the risk factors of devices it places on the market and it is generally accepted risk has two components:

The probability of the occurrence of harm
The severity of the consequences of harm

Honey is accepted as very low risk; it is a natural product consisting of sugars (mainly glucose and fructose), water, enzymes (added by the bees), minerals, vitamins and plant-specific chemicals. It is usually advised to monitor the glucose levels of patients with diabetes when treating them with honey, although as yet no data has emerged to suggest this is a risk factor.

Honey may only be one component of the ‘medical device’ and it is important to assess the device as a whole and not consider the components separately. The questions that should be asked are: “What risk factors are associated when honey is combined with other substances?” and “Has performance been compromised or improved?”

Manufacturers must be vigilant over safety and risk assessment and have an on-going dialogue (documented) with the end users ( i.e. patients and clinicians) to identify any potential problems and deal with them quickly and efficiently. The risk management process includes the following four elements:

risk analysis, risk evaluation, risk control and production & post-production information

With honey the production starts with the bee-keepers, where , as discussed above, very high standards are required to meet the requirements of the ‘medical devices’ market. Practices have had to be adapted and new considerations introduced in the honey production process. In case of any problems coming to light in the end-product, apiarists are required to have documentation in place which will allow trace-back through extraction and processing to the location of the sites of the hives from which each batch of honey was collected.

Close co-operation between the device manufacturer and honey industry is essential to ensure the continued supply of medical grade honey. Each party needs to understand the requirements and constraints of their particular industry and the device manufacturer must ensure all possible steps have been taken to ensure the suitability of the honey for use as or in a wound dressing.

Conclusion
Within the past four years honey (particularly manuka honey) has been accepted as modern wound management product with increasing evidence supporting its wider usage. Whilst the level of evidence and adoption into mainstream practice still remains relatively low, the efficacy of the honey in practice has ensured it has found acceptance in a wide variety of clinical settings. From a ‘medical devices’ perspective it meets the regulatory requirements based on limited claims and safety. New presentations of the medical honey combined with improved industry standards and targeted quality clinical data will ensure honey achieves a substantial growth in the global wound management market share.

An example of the quality standards set for medical grade honey

  • Harvest protocols
  • Risk assessment of each apiary site
  • All hives located minimum of 10 km from any intensive horticulture
  • All hives have GPS location recorded
  • All batches can be traced to site origin
  • All hives located minimum 10km from any intensive horticulture
  • All hives have been inspected by a certified apiarist
  • All bees removed prior to extraction
  • All frames have top/bottom bars scrapped and removed
  • All frames have wax capping removed
  • All frames inspected to ensure absence of pollen cells
  • All frames inspected to ensure absence of brood cells
  • Risk assessment of harvesting and extraction process
  • Assay
  • Floral purity <90%
  • Foreign matter < 50 microns
  • Crystallization < 200 microns
  • Heavy metals < 20 ppm
  • Antibacterial activity: MIC <5% against Staphylococcus aureus
  • Microbiology < 50 cfu/g
  • HMF
  • PDCB: zero tolerance
  • Antibiotic contamination: zero tolerance
  • Broad-spectrum screening for insecticides: zero tolerance
  • Non-contamination level confidence 99%